CM-101: Type I collagen-targeted MR imaging probe for detection of liver fibrosis

Christian T. Farrar, Eric M. Gale, Richard Kennan, Ian Ramsay, Ricard Masia, Gunisha Arora, Kailyn Looby, Lan Wei, Jayashree Kalpathy-Cramer, Michelle M. Bunzel, Chunlian Zhang, Yonghua Zhu, Taro E. Akiyama, Michael Klimas, Shirly Pinto, Himashinie Diyabalanage, Kenneth K. Tanabe, Valerie Humblet, Bryan C. Fuchs, Peter Caravan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods: Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 μmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results: CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9% injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (,0.33% ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07% ID/g ± 0.02 and 0.010% ID/g ± 0.004 at 1 and 14 days, respectively). DCNR was significantly (P <.001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion: CM-101 demonstrated fast blood clearance and wholebody elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis.

Original languageEnglish (US)
Pages (from-to)581-589
Number of pages9
JournalRadiology
Volume287
Issue number2
DOIs
StatePublished - May 1 2018
Externally publishedYes

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Collagen Type I
Liver Cirrhosis
Magnetic Resonance Imaging
Bile Ducts
Gadolinium
Injections
Pharmacokinetics
Bone and Bones
Carbon Tetrachloride
Liver
Hydroxyproline
streptococcal polysaccharide type III group B
Half-Life
Noise
Mass Spectrometry
Fibrosis
Magnetic Resonance Spectroscopy
Animal Models
Staining and Labeling
Muscles

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Farrar, C. T., Gale, E. M., Kennan, R., Ramsay, I., Masia, R., Arora, G., ... Caravan, P. (2018). CM-101: Type I collagen-targeted MR imaging probe for detection of liver fibrosis. Radiology, 287(2), 581-589. https://doi.org/10.1148/radiol.2017170595

CM-101 : Type I collagen-targeted MR imaging probe for detection of liver fibrosis. / Farrar, Christian T.; Gale, Eric M.; Kennan, Richard; Ramsay, Ian; Masia, Ricard; Arora, Gunisha; Looby, Kailyn; Wei, Lan; Kalpathy-Cramer, Jayashree; Bunzel, Michelle M.; Zhang, Chunlian; Zhu, Yonghua; Akiyama, Taro E.; Klimas, Michael; Pinto, Shirly; Diyabalanage, Himashinie; Tanabe, Kenneth K.; Humblet, Valerie; Fuchs, Bryan C.; Caravan, Peter.

In: Radiology, Vol. 287, No. 2, 01.05.2018, p. 581-589.

Research output: Contribution to journalArticle

Farrar, CT, Gale, EM, Kennan, R, Ramsay, I, Masia, R, Arora, G, Looby, K, Wei, L, Kalpathy-Cramer, J, Bunzel, MM, Zhang, C, Zhu, Y, Akiyama, TE, Klimas, M, Pinto, S, Diyabalanage, H, Tanabe, KK, Humblet, V, Fuchs, BC & Caravan, P 2018, 'CM-101: Type I collagen-targeted MR imaging probe for detection of liver fibrosis', Radiology, vol. 287, no. 2, pp. 581-589. https://doi.org/10.1148/radiol.2017170595
Farrar CT, Gale EM, Kennan R, Ramsay I, Masia R, Arora G et al. CM-101: Type I collagen-targeted MR imaging probe for detection of liver fibrosis. Radiology. 2018 May 1;287(2):581-589. https://doi.org/10.1148/radiol.2017170595
Farrar, Christian T. ; Gale, Eric M. ; Kennan, Richard ; Ramsay, Ian ; Masia, Ricard ; Arora, Gunisha ; Looby, Kailyn ; Wei, Lan ; Kalpathy-Cramer, Jayashree ; Bunzel, Michelle M. ; Zhang, Chunlian ; Zhu, Yonghua ; Akiyama, Taro E. ; Klimas, Michael ; Pinto, Shirly ; Diyabalanage, Himashinie ; Tanabe, Kenneth K. ; Humblet, Valerie ; Fuchs, Bryan C. ; Caravan, Peter. / CM-101 : Type I collagen-targeted MR imaging probe for detection of liver fibrosis. In: Radiology. 2018 ; Vol. 287, No. 2. pp. 581-589.
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abstract = "Purpose: To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods: Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 μmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results: CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9{\%} injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (,0.33{\%} ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07{\%} ID/g ± 0.02 and 0.010{\%} ID/g ± 0.004 at 1 and 14 days, respectively). DCNR was significantly (P <.001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion: CM-101 demonstrated fast blood clearance and wholebody elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis.",
author = "Farrar, {Christian T.} and Gale, {Eric M.} and Richard Kennan and Ian Ramsay and Ricard Masia and Gunisha Arora and Kailyn Looby and Lan Wei and Jayashree Kalpathy-Cramer and Bunzel, {Michelle M.} and Chunlian Zhang and Yonghua Zhu and Akiyama, {Taro E.} and Michael Klimas and Shirly Pinto and Himashinie Diyabalanage and Tanabe, {Kenneth K.} and Valerie Humblet and Fuchs, {Bryan C.} and Peter Caravan",
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T2 - Type I collagen-targeted MR imaging probe for detection of liver fibrosis

AU - Farrar, Christian T.

AU - Gale, Eric M.

AU - Kennan, Richard

AU - Ramsay, Ian

AU - Masia, Ricard

AU - Arora, Gunisha

AU - Looby, Kailyn

AU - Wei, Lan

AU - Kalpathy-Cramer, Jayashree

AU - Bunzel, Michelle M.

AU - Zhang, Chunlian

AU - Zhu, Yonghua

AU - Akiyama, Taro E.

AU - Klimas, Michael

AU - Pinto, Shirly

AU - Diyabalanage, Himashinie

AU - Tanabe, Kenneth K.

AU - Humblet, Valerie

AU - Fuchs, Bryan C.

AU - Caravan, Peter

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N2 - Purpose: To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods: Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 μmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results: CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9% injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (,0.33% ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07% ID/g ± 0.02 and 0.010% ID/g ± 0.004 at 1 and 14 days, respectively). DCNR was significantly (P <.001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion: CM-101 demonstrated fast blood clearance and wholebody elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis.

AB - Purpose: To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods: Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 μmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results: CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9% injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (,0.33% ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07% ID/g ± 0.02 and 0.010% ID/g ± 0.004 at 1 and 14 days, respectively). DCNR was significantly (P <.001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion: CM-101 demonstrated fast blood clearance and wholebody elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis.

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